Printer Friendly

Borrelia crocidurae meningoencephalitis, West Africa.

Tick-borne relapsing fever (TBRF) is caused by several Borrelia species that are transmitted through the bites of Ornithodoros ticks (1). TBRF is an acute febrile illness characterized by multiple recurrences of nonspecific signs and symptoms, including fever, headache, myalgia, and arthralgia. Neurologic complications might occur, particularly related to B. hispanica, B. crocidurae, B. duttoni, and B. turicatae infections (2-7). Conventional diagnosis is made by microscopic detection of spirochetes in blood samples collected during acute febrile episodes and by direct examination of the cerebral spinal fluid (CSF) of patients with neurologic manifestations. Recently, molecular methods have been shown to be more reliable for Borrelia spp. detection in blood and CSF (3,8). B. crocidurae is endemic to West Africa; in Senegal, the rising incidence of infections reported recently has been associated with climate change (1,9). We report 3 cases of meningitis and 2 cases of encephalitis in 4 persons among a total of 11 consecutive travelers who returned from West Africa to France with B. crocidurae infections.

The Study

Persons included in our study had clinical signs and symptoms of meningitis or encephalitis, or both, and were selected from the 11 patients with cases of B. crocidurae TBRF that were reported to and confirmed by the National Reference Center for Borrelia (NRCB) in France during 2009-2011. The NRCB is the reference laboratory responsible for the epidemiologic surveillance of TBRF in France. Clinical meningitis or encephalitis was defined as previously reported (2). Borrelia species were detected in Giemsa-stained thin blood smears by microscopy and quantitative buffy coat analysis (Becton Dickinson, Le Pont de Claix, France) when available (4). Borrelia spp. were detected and identified by using 16SrRNA PCR and subsequent sequencing as described (8). We tested serum and CSF samples with standardized antibody assays for detection of Borrelia spp. that cause Lyme disease (Table).

Among the 11 TBRF cases reported to NRCB during the 3-year study, we identified 4 (36%) cases of clinical meningitis or encephalitis, or both. The epidemiologic, clinical, and laboratory findings and the treatment of the 4 patients are documented in the Table. Three of the 4 patients were adult men, 26-57 years of age, and 1 was a 7-year-old girl. None of the patients were immunocompromised. They were all given appropriate antimalarial chemoprophylaxis. Patients 1 and 4 experienced their first febrile episode in Africa and were empirically treated with antimalarial drugs without biological confirmation of Plasmodium infection.

At the time of admission to health care facilities, all patients had fever and headache. Patients 2, 3, and 4 had signs of meningitis, including neck stiffness; patients 2 and 4 also had phonophobia and photophobia. Patients 1 and 4 had encephalitis with drowsiness, which for patient 4 was accompanied by cerebellar syndrome (dysarthria and dysmetria). All patients except patient 3 underwent computed tomography scanning of the brain; no abnormality was detected. The 2 patients with encephalitis were examined by magnetic resonance imaging; in patient 4, a predominant positive contrast of the cerebellum leptomeninges on the right side was observed.

For all patients, 16S rRNA PCR and sequencing identified B. crocidurae (8) in blood samples. Laboratory analysis of the 4 CSF samples showed a lymphocytic pleocytosis, high protein concentrations, and a glucose value within reference range (Table). The molecular methods applied to CSF samples confirmed neurologic B. crocidurae infection in patients 1, 2, and 3. Serum samples collected from patients 1 and 4 at the time of diagnosis were tested by using Lyme disease serodiagnostic assays. ELISA detected substantial levels of IgM and IgG in samples from both patients; 1 was confirmed by Western blot analysis. The CSF sample from patient 4 showed a low level of IgG (Table).

All cases were treated with doxycycline or ceftriaxone, or both (Table). In all patients, fever resolved within 3 days of the beginning of the appropriate treatment, and the outcomes were favorable. No Jarisch-Herxheimer reaction was observed.

B. crocidurae-associated TBRF is an emerging disease that is considered to be benign (1,9). However, the series of infections reported here suggest that severe neurologic complications, notably, meningitis and encephalitis, occur more frequently than previously thought and could be particularly common in travelers who acquired this infection in West Africa. For the patients we studied, the earliest neurologic signs occurred during the second febrile episode, confirming previous studies reporting the onset of neurologic complications after the first episode (2). However, facial palsy, often considered to be among the main clinical signs and symptoms of neuroborreliosis caused by TBRF-associated Borrelia species, was not observed in these patients (2). A similar clinical manifestation described in a recent case report of B. crocidurae encephalitis is entirely consistent with our observations (3).

Functional and experimental studies have focused on the capacity of TBRF-associated Borrelia species to cross the blood-brain barrier and to persist in the brain (2-7,10,11). These studies have established B. crocidurae as the most neurotropic species, an observation consistent with this and other case series and case reports. In animal models, this feature has been associated with the presence of vascular microemboli in the brain of infected animals and the particular ability of B. crocidurae to form and bind to erythrocyte rosettes, a phenomenon also involved in cerebral malaria pathogenesis. Erythrocyte aggregation might prevent host-pathogen interactions and thereby protect the spirochetes from the specific immune response (10,12,13).

The rather high frequency and severity of neurologic complications associated with B. crocidurae infection raise the problem of distinguishing it from cerebral malaria, because the areas of endemicity of these 2 diseases largely coincide (1,9). Indeed, relapsing fever is frequently misdiagnosed as malaria, as it was for 2 of the patients we studied, who were initially treated with antimalarial drugs (14). In this context, quantitative buffy coat analysis that can effectively detect each pathogen in blood might be of particular interest (4). In addition, our study confirms the usefulness of molecular methods applied to blood and CSF samples to confirm Borrelia infection (3,8). The negative result obtained by PCR of CSF from patient 4 could have been the consequence of inappropriate storage of the sample at high room temperature for 72 hours before analysis.

Lyme disease serodiagnostic testing of serum and CSF samples might be helpful. Indeed, cross-reacting IgG and IgM were detected by ELISAs and in Western blot assays. Because Lyme disease is endemic to France, our results could have been caused by the actual detection of B. burgdorferi sensu lato antibodies, although none of the patients had a known history of Lyme disease.

No specific recommendations have been proposed for the treatment of patients with TBRF neuroborreliosis. Erythromycin and penicillin have been reported to be ineffective (5,6). In our series, all patients were prescribed either ceftriaxone or doxycycline, or both (Table), resulting in successful treatment of the disease. Thus, from the literature and our own experience, we suggest that TBRF with neurologic involvement should be treated with ceftriaxone or doxycycline for at least 21 days.

Conclusions

Our study highlights the frequent occurrence of meningitis or encephalitis in patients with B. crocidurae TBRF acquired in West Africa. The clinical and radiologic manifestations suggest that this infection could be more severe than previously thought. Consequently, travelers returning from West Africa with febrile neurologic disorders should be tested immediately for biological confirmation of Borrelia infection through blood and CSF analyses, including molecular methods.

Acknowledgments

We thank Laurence Courdavault, Patrick Plesiat, Ian Dorval, Jacques Croize, and the technicians of the biology laboratory of the Centre Hospitalier d'Argenteuil for their help with diagnostic confirmation and for providing samples from the patients. We also thank Olivier Epaulard for his insightful comments on the manuscript.

Dr Goutier is an infectious disease specialist at the Groupe Hospitalier Mutualiste in Grenoble, France. Her research interests include clinical infectious diseases, antimicrobial drugs resistance, and epidemiology of nosocomial pathogens.

References

(1.) Cutler SJ, Abdissa A, Trape J-F. New concepts for the old challenge of African relapsing fever borreliosis. Clin Microbiol Infect. 2009;15:400-6. http://dx.doi.org/10.1111/j.1469-0691.2009.02819.x

(2.) Cadavid D, Barbour AG. Neuroborreliosis during relapsing fever: review of the clinical manifestations, pathology, and treatment of infections in humans and experimental animals. Clin Infect Dis. 1998;26:151-64. http://dx.doi.org/10.1086/516276

(3.) Bottieau E, Verbruggen E, Aubry C, Socolovschi C, Vlieghe E. Meningoencephalitis complicating relapsing fever in traveler returning from Senegal. Emerg Infect Dis. 2012;18:697-8. http://dx.doi. org/10.3201/eid1804.111771

(4.) van Dam AP, van Gool T, Wetsteyn JC, Dankert J. Tick-borne relapsing fever imported from West Africa: diagnosis by quantitative buffy coat analysis and in vitro culture of Borrelia crocidurae. J Clin Microbiol. 1999;37:2027-30.

(5.) Colebunders R, De Serrano P, Van Gompel A, Wynants H, Blot K, Van den Enden E, et al. Imported relapsing fever in European tourists. Scand J Infect Dis. 1993;25:533-6. http://dx.doi. org/10.3109/00365549309008539

(6.) Nassif X, Dupont B, Fleury J, Lapresle C. Ceftriaxone in relapsing fever. Lancet. 1988;332:394. http://dx.doi.org/10.1016/S0140-6736(88)92860-7

(7.) Rodhain F. Borrelia et fievres recurrentes: aspects epidemiologiques actuels. Bull Inst Pasteur. 1976;74:173-218.

(8.) Sarih M, Garnier M, Boudebouch N, Bouattour A, Rihani A, Hassar M, et al. Borrelia hispanica relapsing fever, Morocco. Emerg Infect Dis. 2009;15:1626-9. http://dx.doi.org/10.3201/eid1510.090403

(9.) Vial L, Diatta G, Tall A, Ba EH, Bouganali H, Durand P, et al. Incidence of tick-borne relapsing fever in west Africa: longitudinal study. Lancet. 2006;368:37-43. http://dx.doi.org/10.1016/S0140-6736(06)68968-X

(10.) Nordstrand A, Barbour AG, Bergstrom S. Borrelia pathogenesis research in the post-genomic and post-vaccine era. Curr Opin Microbiol. 2000;3:86-92. http://dx.doi.org/10.1016/S1369-5274(99)00056-9

(11.) Charmot G, Rodhain F, Dupont B, Sansonetti P, Lapresle C. Meningoencephalitis in a repatriate from Senegal. Think of borreliosis [in French]. Presse Med. 1986;15:979.

(12.) Shamaei-Tousi A, Martin P, Bergh A, Burman N, Brannstrom T, Bergstrom S. Erythrocyte-aggregating relapsing fever spirochete Borrelia crocidurae induces formation of microemboli. J Infect Dis. 1999;180:1929-38. http://dx.doi.org/10.1086/315118

(13.) Burman N, Shamaei-Tousi A, Bergstrom S. The spirochete Borrelia crocidurae causes erythrocyte rosetting during relapsing fever. Infect Immun. 1998;66:815-9.

(14.) Nordstrand A, Bunikis I, Larsson C, Tsogbe K, Schwan TG, Nilsson M, et al. Tickborne relapsing fever diagnosis obscured by malaria, Togo. Emerg Infect Dis. 2007;13:117-23. http://dx.doi.org/10.3201/ eid1301.060670

Sandrine Goutier, [1] Elisabeth Ferquel, [1] Claudine Pinel, Annick Bosseray, Bruno Hoen, Gerard Couetdic, Amina Bourahoui, Claire Lapostolle, Herve Pelloux, Martine Garnier, Natacha Sertour, Isabelle Pelloux, Patricia Pavese, and Muriel Cornet

[1] These authors contributed equally to this work.

Author affiliations: Grenoble Teaching Hospital, Grenoble, France (S. Goutier, C. Pinel, A. Bosseray, H. Pelloux, I. Pelloux, P. Pavese, M. Cornet); Pasteur Institute, Paris, France (E. Ferquel, M. Garnier, N. Sertour), Joseph Fourier University, Grenoble (C. Pinel, H. Pelloux, M. Cornet); Besancon Teaching Hospital, Besancon, France (B. Hoen, G. Couetdic); Argenteuil Hospital, Argenteuil, France (A. Bourahoui); and Laennec Hospital, Quimper, France (C. Lapostolle)

DOI: http://dx/doi.org/10.3201/eid1902.121325

Address for correspondence: Sandrine Goutier, Service de Medecine Interne, Groupe Hospitalier Mutualiste de Grenoble, 8 Rue du Docteur Calmette, 38028 Grenoble Cedex 1, France; email: sandrinegoutier@ hotmail.com
Table. Epidemiologic, clinical, and laboratory findings and
treatment for patients with Borrelia crocidurae
meningoencephalitis *

Variables Patient 1 Patient 2

Demographic factor
 Age, y/sex 36/M 57/M
 Country of origin/of Senegal/France France/France
 residence
 Travel country Senegal Senegal
 Travel dates 2009 Mar-May 2010 May
 Travel duration, d 53 15
 Travel accommodation Family house Hotel
 Arthropod or insect bite No Yes
 report
 Individual vector No No

First suspected diagnosis Malaria/quinine Sinusitis
 ([dagger])/ presumptive
 treatment
Symptoms
 Oral temperature Yes Yes
 >38.5[degrees]C
 Chills No No
 Total no. febrile 2/1 4/2
 episodes/no. before
 diagnosis
 Length of acute febrile 2-8 2-6
 episodes, d
 Afebrile periods between 15 2-15
 febrile episodes, d
 Asthenia/anorexia/weight Yes/no/no Yes/yes/yest
 loss
 Headache Yes (severe) Yes
 Myalgia No No
 Photophobia, phonophobia No Yes
 Neck stiffness No Yes
 Cerebellar syndrome No No
 Drowsiness Yes No
Imaging results
 Brain CT scan Normal Normal
 Brain MRI Normal ND
Serologic results
 Leukocytes, g/L 4.7 15.8
 Hemoglobin, g/L 134 139
 Platelets, g/L 245 273
 C-reactive protein, mg/L 103 4
 Creatinine, [micro]mol/L 107 76
 Borrelia spp. detection, +([section]) y+([paragraph])
 Giemsa-stained blood
 smear
 Quantitative buffy coat ND ND
 ELISA anti-B. burgdorferi
 (titer)
 Siemens Enzygnost Lyme +(11.3) ND
 link VlsE/IgG (#)
 Siemens Enzygnost +(3.7) ND
 Borreliosis/IgM (#)
 Western blot anti-B.
 burgdorferi
 Bio-Advance IgG anti +/-/-/+ ND
 -VlsE/p41/p83/p21 (#)
 EUROIMMUN IgG anti-p17/ ND ND
 p19/p21/p25/p30/p31/
 p39/p83/VlsE (#)
 Meridian Bioscience IgM ND ND
 garinii/afzelii/p41/
 p39/p17 (#)
 Bio-Advance IgM +/+ ND
 anti-p25/p83 (#)
 16S rRNA PCR Borrelia/ +/B. crocidurae +/B. crocidurae
 identification
CSF test results
 Leukocytes, 405 217
 cells/[mm.sup.3]
 % Lymphocytes 94 80
 Erythrocytes, 0 7
 cells/[mm.sup.3]
 Protein, g/L 0.66 1.38
 Glucose, mmol/L 3.1 2.7
 Chloride, mmol/L 114 113
 Lactate, mmol/L ND ND
 Direct examination - -
 (Gram stain)
 Conventional bacterial - -
 culture
 16S rRNA PCR Borrelia/ +/B. crocidurae +/B. crocidurae
 identification
 ELISA anti -B. burgdorferi
 Siemens Enzygnost Lyme ND ND
 link VlsE/IgG (#)
 Siemens Enzygnost ND ND
 Borreliosis/IgM (#)
Treatment Ceftriaxone Doxycycline
 (daily dose/total d) (2 g/21) (100 mg
 2xd/10)

Variables Patient 3 Patient 4

Demographic factor
 Age, y/sex 7/F 26/M
 Country of origin/of France/France Senegal/France
 residence
 Travel country Senegal Senegal
 Travel dates 2011 Feb-May 2011 Aug-Sep
 Travel duration, d 15 35
 Travel accommodation Hotel Family house
 Arthropod or insect bite No No
 report
 Individual vector No No

First suspected diagnosis Gastroenteritis Malaria/piperaquin
 ([dagger])/presumptive
 treatment
Symptoms
 Oral temperature Yes Yes
 >38.5[degrees]C
 Chills Yes Yes
 Total no. febrile 6/5 2/1
 episodes/no. before
 diagnosis
 Length of acute febrile 2 2-6
 episodes, d
 Afebrile periods between 2-13 34
 febrile episodes, d
 Asthenia/anorexia/weight Yes/no/no Yes/no/no
 loss
 Headache Yes (severe) Yes (severe)
 Myalgia No Yes
 Photophobia, phonophobia No Yes
 Neck stiffness Yes Yes
 Cerebellar syndrome No Yes
 Drowsiness No Yes
Imaging results
 Brain CT scan ND Normal
 Brain MRI ND Abnormal
Serologic results
 Leukocytes, g/L 13.0 8.4
 Hemoglobin, g/L 115 131
 Platelets, g/L 295 103
 C-reactive protein, mg/L 57 150
 Creatinine, [micro]mol/L 42 99
 Borrelia spp. detection, +([section]) + ([paragraph])
 Giemsa-stained blood
 smear
 Quantitative buffy coat ND +
 ELISA anti-B. burgdorferi
 (titer)
 Siemens Enzygnost Lyme ND +(19)
 link VlsE/IgG (#)
 Siemens Enzygnost ND +(1.21)
 Borreliosis/IgM (#)
 Western blot anti-B.
 burgdorferi
 Bio-Advance IgG anti ND ND
 -VlsE/p41/p83/p21 (#)
 EUROIMMUN IgG anti-p17/ ND -/-/-/-/-/-/-/**/**
 p19/p21/p25/p30/p31/
 p39/p83/VlsE (#)
 Meridian Bioscience IgM ND ND
 garinii/afzelii/p41/
 p39/p17 (#)
 Bio-Advance IgM ND ND
 anti-p25/p83 (#)
 16S rRNA PCR Borrelia/ +/B. crocidurae +/B. crocidurae
 identification
CSF test results
 Leukocytes, 258 156
 cells/[mm.sup.3]
 % Lymphocytes 90 84
 Erythrocytes, 12 5
 cells/[mm.sup.3]
 Protein, g/L 0.39 0.44
 Glucose, mmol/L 2.69 2.9
 Chloride, mmol/L 117 115
 Lactate, mmol/L 1.5 2.2
 Direct examination - -
 (Gram stain)
 Conventional bacterial - -
 culture
 16S rRNA PCR Borrelia/ +/B. crocidurae -
 identification
 ELISA anti -B. burgdorferi
 Siemens Enzygnost Lyme ND - ([double dagger])
 link VlsE/IgG (#)
 Siemens Enzygnost ND -
 Borreliosis/IgM (#)
Treatment Ceftriaxone (2 Doxycycline
 (daily dose/total d) g/14) (100 m 2x d/21),
 ceftriaxon (2 g/15)

* CT, computed tomography; MRI, magnetic resonance imaging; ND, not
done; +, positive; -, negative; CSF, cerebrospinal fluid.

([dagger]) First suspected diagnosis was not biologically confirmed.

([double dagger]) 7 kg in 3 wk.

([section]) Second sample was positive.

([paragraph]) First sample was positive after review prompted by the
quantitative buffy coat result.

(#) Siemens, Erlangen, Germany; Bio-Advance, Bussy Saint Martin,
France; EUROIMMUN Medizinische Labordiagnostika AG, Lubeck, Germany;
Meridian Bioscience, Paris, France.

** Ambiguous.

([dagger][dagger]) At 12-fold dilution (low level).
COPYRIGHT 2013 U.S. National Center for Infectious Diseases
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2013 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:DISPATCHES
Author:Goutier, Sandrine; Ferquel, Elisabeth; Pinel, Claudine; Bosseray, Annick; Hoen, Bruno; Couetdic, Ger
Publication:Emerging Infectious Diseases
Article Type:Disease/Disorder overview
Geographic Code:4EUFR
Date:Feb 1, 2013
Words:2682
Previous Article:Transmission and maintenance cycle of Bartonella quintana among rhesus macaques, China.
Next Article:Influenza A(H5N1) virus surveillance at live poultry markets, Cambodia, 2011.
Topics:

Terms of use | Privacy policy | Copyright © 2020 Farlex, Inc. | Feedback | For webmasters